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Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2

Abstract

THE putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus1-3 by the t(14;18) chromosomal translocation typical of human follicular B-cell lymphomas4. The bcl-2 gene product (refs 5,6) is not altered by the translocation, but its expression is deregulated6–8, presumably by the Igh enhancer Eµ. Constitutive bcl-2 expression seems to augment cell survival, as infection with a bcl-2 retrovirus enables certain growth factor-dependent mouse cell lines to maintain viability when deprived of factor9,10. Furthermore, high levels of the bcl-2 product can protect human B and T lymphoblasts under stress11,12 and thereby confer a growth advantage12–14. Mice expressing a bcl-2 transgene controlled by the Igh enhancer accumulate small non-cycling B cells which survive unusually well in vitro15–17 but do not show a propensity for spontaneous tumorigenesis15,16. In contrast, an analogous myc transgene, designed to mimic the myc–Igh translocation product typical of Burkitt's lymphoma and rodent plasmacytoma18, promotes B lymphoid cell proliferation and predisposes mice to malignancy in pre-B and B lymphoid cells19-22. Previous experiments have suggested that bcl-2 can cooperate with deregulated myc to improve in vitro growth of pre-B and B cells9,11. Here we describe a marked synergy between bcl-2 and myc in doubly transgenic mice. Eµ–bcl–2/myc mice show hyperproliferation of pre-B and B cells and develop tumours much faster than Eµ–myc mice. Surprisingly, the tumours derive from a cell with the hallmarks of a primitive haemopoietic cell, perhaps a lymphoid-committed stem cell.

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References

  1. 1

    Tsujimoto, Y., Finger, L. R., Yunis, J., Nowell, P. C. & Croce, C. M. Science 226, 1097–1099 (1984).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Bakhshi, A. et al. Cell 41, 889–906 (1985).

    Article  Google Scholar 

  3. 3

    Cleary, M. L., Smith, S. D. & Sklar, J. Cell 47, 19–28 (1986).

    CAS  Article  Google Scholar 

  4. 4

    Fukuhara, S., Rowley, J. D., Variakojis, D. & Golomb, H. M. Cancer Res. 39, 3119–3128 (1979).

    CAS  PubMed  Google Scholar 

  5. 5

    Tsujimoto, Y. N., Ikegaki, N. & Croce, C. M. Oncogene 2, 3–7 (1987).

    CAS  PubMed  Google Scholar 

  6. 6

    Chen-Levy, Z., Nourse, J. & Cleary, M. L. Molec. cell. Biol. 9, 701–710 (1989).

    CAS  Article  Google Scholar 

  7. 7

    Reed, J. C., Tsujimoto, Y., Alpers, J. D., Croce, C. M. & Howell, P. C. Science 236, 1295–1299 (1987).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Graninger, W. B., Seto, M., Boutain, B., Goldman, P. & Korsmeyer, S. J. J. clin. Invest. 80, 1512–1515 (1987).

    CAS  Article  Google Scholar 

  9. 9

    Vaux, D. L., Cory, S. & Adams, J. M. Nature 335, 440–442 (1988).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Nunez, G. et al. J. Immun. 144, 3602–3610 (1990).

    CAS  Google Scholar 

  11. 11

    Tsujimoto, Y. Oncogene 4, 1331–1336 (1989).

    CAS  PubMed  Google Scholar 

  12. 12

    Reed, J. C. et al. Proc. natn. Acad. Sci. U.S.A. 87, 3660–3664 (1990).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Reed, J. C., Haldar, S., Cuddy, M. P., Croce, C. M. & Makover, D. Oncogene 4, 1123–1127 (1989).

    CAS  PubMed  Google Scholar 

  14. 14

    Nunez, G. et al. Proc. natn. Acad Sci. U.S.A. 86, 4589–4593 (1989).

    ADS  CAS  Article  Google Scholar 

  15. 15

    McDonnell, T. J. et al. Cell 57, 79–88 (1989).

    CAS  Article  Google Scholar 

  16. 16

    Strasser, A. et al. Curr. Topics Microbiol. Immun. (in the press).

  17. 17

    McDonnell, T. J. et al. Molec. cell. Biol. 10, 1901–1907 (1990).

    CAS  Article  Google Scholar 

  18. 18

    Cory, S. Adv. Cancer Res. 47, 189–234 (1986).

    CAS  Article  Google Scholar 

  19. 19

    Adams, J. M. et al. Nature 318, 533–538 (1985).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Langdon, W. Y., Harris, A. W., Cory, S. & Adams, J. M. Cell 47, 11–18 (1986).

    CAS  Article  Google Scholar 

  21. 21

    Harris, A. W. et al. J. exp. Med. 167, 353–371 (1988).

    CAS  Article  Google Scholar 

  22. 22

    Schmidt, E. V., Pattengale, P. K., Weir, L. & Leder, P. Proc. natn. Acad. Sci. U.S.A. 85, 6047–6051 (1988).

    ADS  CAS  Article  Google Scholar 

  23. 23

    Strasser, A. Eur. J. Immun. 18, 1803–1810 (1988).

    CAS  Article  Google Scholar 

  24. 24

    Spangrude, G. J., Heimfeld, S. & Weissman, I. L. Science 241, 58–62 (1988).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Fredrickson, G. G. & Basch, R. S. J. exp. Med. 169, 1473–1478 (1989).

    Article  Google Scholar 

  26. 26

    Morse, H. C. III et al. J. exp. Med. 165, 920–925 (1987).

    CAS  Article  Google Scholar 

  27. 27

    Palacios, R. & Steinmetz, M. Cell 41, 727–734 (1985).

    CAS  Article  Google Scholar 

  28. 28

    Alessandrini, A., Pierce, J. H., Baltimore, D. & Desiderio, S. V. Proc. natn. Acad. Sci. U.S.A. 84, 1799–1803 (1987).

    ADS  CAS  Article  Google Scholar 

  29. 29

    Sakaguchi, N. & Melchers, F. Nature 324, 579–582 (1986).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Schatz, D. G., Oettinger, M. A. & Baltimore, D. Cell 59, 1035–1048 (1989).

    CAS  Article  Google Scholar 

  31. 31

    Tidmarsh, G. F., Heimfeld, S., Whitlock, C. A., Weissman, I. L. & Müller-Sieburg, C. E. Molec. cell. Biol. 9, 2665–2671 (1989).

    CAS  Article  Google Scholar 

  32. 32

    Langdon, W. L., Harris, A. W. & Cory, S. Oncogene Res. 3, 271–279 (1988).

    CAS  PubMed  Google Scholar 

  33. 33

    Pegoraro, L. et al. Proc. natn. Acad. Sci. U.S.A. 81, 7166–7170 (1984).

    ADS  CAS  Article  Google Scholar 

  34. 34

    Gauwerky, C. E., Haluska, F. G., Tsujimoto, Y., Nowell, P. C. & Croce, C. M. Proc. natn. Acad. Sci. U.S.A. 85, 8548–8552 (1988).

    ADS  CAS  Article  Google Scholar 

  35. 35

    Gauwerky, C. E., Huebner, K., Isobe, M., Nowell, P. C. & Croce, C. M. Proc. natn. Acad. Sci. U.S.A. 86, 8867–8871 (1989).

    ADS  CAS  Article  Google Scholar 

  36. 36

    Aihara, Y., Bühring, H-J., Aihara, M. & Klein, J. Eur. J. Immun. 16, 1391–1399 (1986).

    CAS  Article  Google Scholar 

  37. 37

    Hariharan, I. K. et al. Molec. cell. Biol. 9, 2798–2805 (1989).

    CAS  Article  Google Scholar 

Download references

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Strasser, A., Harris, A., Bath, M. et al. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature 348, 331–333 (1990). https://doi.org/10.1038/348331a0

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